From cell death to embryo arrest: Mathematical models of human preimplantation embryo development

From cell death to embryo arrest: Mathematical models of human preimplantation embryo development
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DOI:
10.1073/pnas.98.4.1655
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发表时间:
2001-02-13
影响因子:
11.1
通讯作者:
Stark, J
Stark, J
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Hardy, K;Spanos, S;Stark, J

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人类植入前胚胎在体外培养的第一周内表现出高水平的凋亡细胞和高速率的发育停止。这两者之间的关系尚不清楚,而且很难用传统的实验方法来确定,部分原因是胚胎数量有限。我们采用实验和数学模型相结合的方法表明,只有当胚胎的发育能力在受精卵阶段已经建立,而环境因素只是调节这一点时,观察到的细胞死亡水平才能与在人类中看到的高水平胚胎停滞相协调。这表明,提高体外受精成功率的研究应该从目前专注于优化培养基转向更多地关注健康受精卵的产生,以及了解在卵裂早期引起染色体和其他异常的机制。
Human preimplantation embryos exhibit high levels of apoptotic cells and high rates of developmental arrest during the first week in vitro. The relation between the two is unclear and difficult to determine by conventional experimental approaches, partly because of limited numbers of embryos. We apply a mixture of experiment and mathematical modeling to show that observed levels of cell death can be reconciled with the high levels of embryo arrest seen in the human only if the developmental competence of embryos is already established at the zygote stage, and environmental factors merely modulate this. This suggests that research on improving in vitro fertilization success rates should move from its current concentration on optimizing culture media to focus more on the generation of a healthy zygote and on understanding the mechanisms that cause chromosomal and other abnormalities during early cleavage stages.